Volatile anesthetic agents and hypoxic ventilatory responses in humans

Control of breathing in humans is regulated through a network of different nervous and chemical mechanisms, in the central nervous system as well as in peripheral structures. One important stimulus for this control is the decrease in arterial oxygen tension, PaO2, in blood, which leads to an increased ventilation. Earlier studies have shown, that anesthetic levels of volatile anesthetic agents abolish the hypoxic ventilatory responses (HVR) in humans. The main aims of the present thesis were: to find out if acute HVR was abolished during isoflurane anesthesia and to determine if the awake biphasic ventilatory response to sustained isocapnic hypoxia was persistent during isoflurane and sevoflurane anesthesia and to quantify the extent of depression of these agents on both acute and sustained isocapnic HVR's. Influences of anesthetic and subanesthetic (sedation) levels of volatile anesthetic agents were investigated on healthy female patients (n = 38) and female (n = 8) and male (n = 8) volunteers. The studies were performed with both poikilocapnic and isocapnic hypoxic provocation techniques. Hypoxia was always introduced rapidly with one abrupt step from normoxia to hypoxia. Both acute and sustained ventilatory responses were investigated. All individual awake and anesthetized or sedated studies were performed on the same day during the same session with the awake study always before the anesthetized or sedated. In the awake state, ventilation variables were recorded with the subjects breathing normally through a transparent tight-fitting face mask covering nose and mouth. Anesthesia was induced by propofol. A free airway was secured and the patients were allowed to resume spontaneous breathing via a non-rebreathing anesthesia circuit. Measurements during anesthesia were performed after at least 45 minutes of isoflurane or sevoflurane administration for equilibration. In all studies an in-line infra-red capnometer and a pneumotachograph were placed in the circuit dead-space. Minute ventilation (VE) was measured by integration of the flow signal from the pneumotachograph. Flow (V), tidal volume (VT) and end-tidal CO2-tension (PECO2) were recorded. Inspired and expired concentrations Of CO2 and O2 as well as inspired and expired concentrations of isoflurane and sevoflurane were continuously recorded along with percutaneous oxygen saturation (SpO2), heart rate (HR) and respiratory rate (RR). The most important finding in this thesis was that hypoxic ventilatory responses are maintained but depressed by anesthetic levels of isoflurane and sevoflurane using isocapnic hypoxic provocations. When a poikilocapnic hypoxic challenge was studied hypoxic ventilatory responses were, however, unaffected by isoflurane anesthesia. The awake biphasic ventilatory response to hypoxia was maintained during anesthesia